Inhibitors Of Corneal Inflammation And Angiogenesis
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Inhibitors Of Corneal Inflammation And Angiogenesis
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Author : Pierfrancesco Mirabelli
language : en
Publisher: Linköping University Electronic Press
Release Date : 2019-04-30
Inhibitors Of Corneal Inflammation And Angiogenesis written by Pierfrancesco Mirabelli and has been published by Linköping University Electronic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-04-30 with categories.
Pathologic angiogenesis is involved in cancer and several blinding conditions such as wet age-related macular degeneration, proliferative retinopathies and corneal neovascularization. In these dieseases, the angiogenic triggers are hypoxia and inflammation, and both involve the main angiogenic mediator, which is Vascular Endothelial Growth Factor (VEGF). Among available treatments, anti-VEGF often shows limited or temporary efficacy, while steroids are potentially responsible for many side-effects. This thesis presents a series of linked studies aimed at elucidating the early pathologic changes leading to inflammation and corneal neovascularization, and how various treatments affect this process. In this thesis, anti-inflammatory and anti-angiogenic treatments are applied in corneal neovascularization models, to identify VEGF-independent pathways and other novel factors as future therapy targets, as well as to investigate the endogenous modulation of angiogenesis. A model of experimental neovascularization in the rat cornea was used as main model, where the neovascular response is triggered by a surgical suture placed into the cornea. Investigational treatments (anti-Vegf, dexamethasone, IMD0354, Gap27, or control substances) were then given topically, with the exception of IMD0354, which was given systemically. The effects in the cornea were studied in vivo with slit lamp photography to assess and quantify macroscopic vessel growth and using in vivo confocal microscopy (IVCM) to study cell infiltration and limbal vessel dilation and detect microscopic vessel sprouts; these examinations were performed longitudinally. Genomic analysis with RNA microarray, selected gene expression with q-RT-PCR, and selected protein expression in tissue (immunohistochemistry, immunofluorescence, Western blot) were performed at different time-points. Moreover, other experiments on cell cultures (HUVEC and HCEC), organ cultures (human corneas), ex vivo models (aortic rings) and in vivo studies (zebrafish vasculogenesis) were performed. Dexamethasone suppressed limbal vasodilation and corneal neovascularization more than anti-Vegf, despite no difference in inflammatory cell infiltration into the cornea. Five-hundred eleven fewer genes were differentially expressed in dexamethasone-treated corneas relative to naïve corneas, compared to anti-Vegf. Among them, several major pro-angiogenic and pro-inflammatory factors and chemokines were suppressed only by dexamethasone and represent novel candidate factors to target in order to improve anti-VEGF treatment. On the other hand, selective inhibition of a single inflammatory pathway (NF-?B), despite showing similar early effects as dexamethasone in suppressing tissue inflammation, was not effective enough to suppress new vessel growth. The same factors suppressed by dexamethasone are also inhibited in endogenous modulation of angiogenesis. Surprisingly, dexamethasone activated several complement factors, which could possibly be beneficial in the anti-angiogenic response. In a different therapeutic approach, promoting cell migration to accelerate epithelial wound closure similarly was not sufficient to avoid inflammation and angiogenesis in the cornea. In conclusion, new and more effective treatments are needed for corneal inflammation and neovascularization with fewer side-effects. In this thesis, several novel factors and mechanisms related to inflammation are identified, factors that are not addressed by anti-Vegf therapy, and therefore represent interesting objects for further study, as they have the potential to be targets for adjuvant therapy. Specific anti-inflammatory treatment as well as therapeutic activation of endogenous regulatory pathways, and potentially complement modulation, might represent new strategies to improve anti-angiogenic therapy, but when used alone they do not seem to avoid corneal neovascularization.
Regulation Of Inflammation And Angiogenesis In The Cornea
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Author : Anthony Mukwaya
language : en
Publisher: Linköping University Electronic Press
Release Date : 2018-05-21
Regulation Of Inflammation And Angiogenesis In The Cornea written by Anthony Mukwaya and has been published by Linköping University Electronic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-05-21 with categories.
Inflammation and angiogenesis, the growth of new blood vessels from pre-existing ones, are involved in tumor growth, ocular diseases and wound healing. In ocular angiogenesis, new pathological vessels grow into a specific eye tissue, leak fluid, and disrupt vision. The development of safe and effective therapies for ocular angiogenesis is of great importance for preventing blindness, given that current treatments have limited efficacy or are associated with undesirable side effects. The search for alternative treatment targets requires a deeper understanding of inflammation and how it can lead to angiogenesis in the eye in pathologic situations. This thesis provides new insights into the regulation of inflammation and angiogenesis, particularly at the gene expression and phenotypic levels, in different situations characterized by angiogenesis of the cornea, often called corneal neovascularization. For instance, specific genes and pathways are either endogenously activated or suppressed during active inflammation, wound healing, and during resolution of inflammation and angiogenesis, serving as potential targets to modulate the inflammatory and angiogenic response. In addition, as part of the healing response to restore corneal transparency, inflammation and angiogenesis subside with time in the cornea. In this context, LXR/RXR signaling was found to be activated in a time-dependent manner, to potentially regulate resolution of inflammation and angiogenesis. During regression of new angiogenic capillaries, ghost vessels and empty basement membrane sleeves are formed, which can persist in the cornea for a long time. Here, ghost vessels were found to facilitate subsequent revascularization of the cornea, while empty basement membrane sleeves did not revascularize. The revascularization response observed here was characterised by vasodilation, increased inflammatory cell infiltration and by sprouting at the front of the reperfused vessels. Importantly, reactive oxygen species and nitrous oxide signaling among other pro-inflammatory pathways were activated, and at the same time anti-inflammatory LXR/RXR signaling was inhibited. The interplay between activation and inhibition of these pathways highlights potential mechanisms that regulate corneal revascularization. When treating corneal neovascularization clinically, corticosteroids are in widespread use due to their effectiveness. To minimize the many undesirable side effects associated with corticosteroid use, however, identifying new and more selective agents is of great importance. Here, it was observed that corticosteroids not only suppressed pro-inflammatory chemokines and cytokines, but also activated the classical complement pathway. Classical complement may represent a candidate for further selective therapeutic manipulation to investigate its effect on treatment of corneal neovascularization. In summary, this thesis identifies genes, pathways, and phenotypic responses involved in sprouting and remodeling of corneal capillaries, highlights novel pathways and factors that may regulate inflammation and angiogenesis in the cornea, and provides insights into regulation of capillary regression and reactivation. Further investigation of these regulatory mechanisms may offer alternative and effective treatment targets for the treatment of corneal inflammation and angiogenesis.
Corneal Angiogenesis
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Author : Gordon K. Klintworth
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Corneal Angiogenesis written by Gordon K. Klintworth and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
In this research monograph, the noted scholar Dr. Gordon K. Klintworth brings together all the available information on the pathogenesis of corneal neovascularization. This book should be a valuable contribution to the medical literature of ophthalmology and clinical pathology. Despite its relatively simple structure the cornea possesses many unique properties. These attributes include its crystal clarity and avascularity in the health state. This normally transparent structure has been the focal point for Dr. Klintworth's research endeavors for more than two decades. This monograph summarizes current knowledge about angiogenesis within this tissue as well as information about the related issue of the cornea's normal avascularity. The text provides a comprehensive overview of the topic based on studies by a large number of investigators who were either concerned with corneal neovascularization in particular or angiogenesis in general.
Ocular Angiogenesis
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Author : Joyce Tombran-Tink
language : en
Publisher: Springer Science & Business Media
Release Date : 2007-11-06
Ocular Angiogenesis written by Joyce Tombran-Tink and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007-11-06 with Medical categories.
Leading academic and pharmaceutical researchers and clinicians from many disciplines synthesize and summarize current clinical and basic knowledge concerning abnormal growth of blood vessels in the eye, the cause of major neovascular eye diseases. The authors also identify and assess the most promising approaches with potential for commercial exploitation and discuss the challenges encountered in developing therapeutics for ocular neovascular diseases. Highlights include illuminating chapters on gene therapy and novel drug delivery systems and excellent summaries of the newest therapeutic approaches.
Ctla 2 Alpha Is A Potent Inhibitor Of Angiogenesis In Murine Ocular Tissue
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Author : Kazuichi Maruyama
language : en
Publisher:
Release Date : 2021
Ctla 2 Alpha Is A Potent Inhibitor Of Angiogenesis In Murine Ocular Tissue written by Kazuichi Maruyama and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2021 with categories.
Abstract: Cytotoxic T lymphocyte antigen-2 (CTLA-2) alpha has been reported to suppress the activities of cathepsin L (Cath L), which is deeply involved in angiogenesis. Therefore, we assessed whether CTLA-2 alpha plays a role in angiogenesis in ocular tissue. To establish models of corneal inflammation and experimental choroidal neovascularization (CNV), male C57BL/6J mice (n = 5) underwent corneal suture placement or laser-induced CNV, respectively. Mice were then injected with recombinant CTLA-2 alpha (1 μg) into the peritoneal cavity at day 0 and every 2 days after operation. In vitro experiments were performed to assess the inflammatory response by measuring TNF-alpha secretion in peritoneal cavity exudate cells (PECs) or the proliferation of mouse vascular endothelial cells (mVECs). CTLA-2 alpha treatment dramatically suppressed corneal angiogenesis, as well as laser-induced CNV. Moreover, CTLA-2 alpha inhibited the proliferation of mVECs in vitro, while CTLA-2 alpha abolishment was able to rescue proliferation. However, CTLA-2 alpha could not suppress cytokine secretion from inflammatory cells such as PECs. In summary, CTLA-2 alpha was able to suppress angiogenesis by suppressing endothelial cell proliferation. Further studies are needed to investigate its usefulness as a new antiangiogenic treatment for a variety of conditions, including age-related macular degeneration
Physiologic And Pathologic Angiogenesis
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Author : Dan Simionescu
language : en
Publisher: BoD – Books on Demand
Release Date : 2017-04-05
Physiologic And Pathologic Angiogenesis written by Dan Simionescu and has been published by BoD – Books on Demand this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-04-05 with Medical categories.
The purpose of this book is to highlight novel advances in the field and to incentivize scientists from a variety of fields to pursue angiogenesis as a research avenue. Blood vessel formation and maturation to capillaries, arteries, or veins is a fascinating area which can appeal to multiple scientists, students, and professors alike. Angiogenesis is relevant to medicine, engineering, pharmacology, and pathology and to the many patients suffering from blood vessel diseases and cancer, among others. We are hoping that this book will become a source of inspiration and novel ideas for all.
Immunology Inflammation And Diseases Of The Eye
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Author : Darlene A. Dartt
language : en
Publisher: Academic Press
Release Date : 2011-02-26
Immunology Inflammation And Diseases Of The Eye written by Darlene A. Dartt and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-02-26 with Medical categories.
This selection of articles from the Encyclopedia of the Eye provides a comprehensive overview of immunological features, diseases and inflammation of the eye and its support structures and organs. Rather than taking an immunological focus that is strictly suitable for clinicians, the volume offers a considerable basic science background and addresses a broad range of topics - the immune system of the eye, its various disorders, mechanisms of inflammation of the eye and visual system, treatment, wound healing mechanisms, stem cells, and more. The first single volume to integrate comparative studies into a comprehensive resource on the neuroscience of ocular immunology Chapters are carefully selected from the Encyclopedia of the Eye by the world's leading vision researchers The best researchers in the field provide their conclusions in the context of the latest experimental results
Clinical Ocular Toxicology
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Author : Frederick T. Fraunfelder
language : en
Publisher: Saunders
Release Date : 2008
Clinical Ocular Toxicology written by Frederick T. Fraunfelder and has been published by Saunders this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with Medical categories.
Written by international authorities in ocular toxicology, including the Founder of The National Registry of Drug-Induced Side Effects and its current Director, this essential resource provides the clinically relevant information you need to effectively diagnose and manage herbal, chemical, and drug-related ocular problems. Comprehensive coverage of all drugs' generic and trade drug names, primary uses, ocular and systemic side effects, and clinical significance make this book - like its best-selling predecessor, Drug-Induced Ocular Side Effects - the ideal reference for quick, on-the-spot consultation. Leaders in the field provide need-to-know information on all aspects of ocular toxicology-all in one concise reference. Data from the National Registry of Drug Induced Ocular Side-Effects (Casey Eye Institute, Portland, OR) and the World Health Organization (Uppsala, Sweden) help you recognize and avoid drug-induced ocular side effects. A highly templated format makes retrieval of essential knowledge quick and easy. A wealth of full-color photographs provide vivid, visual diagnostic guidance. The latest information on approved medications helps you stay up to date and provide state-of-the-art care. Extensive coverage of principles of therapy, ocular drug delivery, methods to evaluate drug-induced visual side effects, and the role of electrophysiology and psychophysics gives you the knowledge you need to manage any challenge in ocular toxicology Authoritative guidance on ocular drugs and their use in pregnancy helps you safely manage the unique needs of these patients. The inclusion of the WHO classification system helps you determine whether a particular side effect is certain, probable, or likely to occur.
Retinal And Choroidal Angiogenesis
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Author : John Penn
language : en
Publisher: Springer Science & Business Media
Release Date : 2008-01-19
Retinal And Choroidal Angiogenesis written by John Penn and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-01-19 with Medical categories.
This book provides a comprehensive, in-depth review of our current understanding of the growth of blood vessels within the eye. Novel therapeutic strategies for the treatment of ocular angiogenesis are discussed, as are the unique challenges presented by delivery of drugs to the eye. The book emphasizes basic principles rather than specific experimental results, although recently acquired data is frequently cited to illustrate points of broader theoretical significance.
The Textbook Of Angiogenesis And Lymphangiogenesis Methods And Applications
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Author : Enrique Zudaire
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-11-29
The Textbook Of Angiogenesis And Lymphangiogenesis Methods And Applications written by Enrique Zudaire and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-11-29 with Medical categories.
Angiogenesis and lymphangiogenesis have become attractive targets for drug therapy because of their key roles in a broad spectrum of pathological disease states ranging from macular degeneration to tumor growth and metastasis. A substantial increase in the research effort over the past decade has deepened our understanding of the basic mechanisms underlying angiogenesis and lymphangiogenesis, promoting the development of promising therapeutics for the clinical management of vascular-related diseases. These extraordinary advancements have been built upon a vast array of diverse analytical techniques developed globally throughout the field. Over the years, these methods have evolved to suit the specific needs of different researchers and experimental scenarios, resulting in a myriad of technical variants of basic assay approaches. "The Textbook of Angiogenesis and Lymphangiogenesis: Methods and Applications" is an up-to-date comprehensive textbook on angiogenesis and lymphangiogenesis techniques and applications. This volume is designed to embody the collective works of experts in the clinical as well as the basic research arenas who have significantly contributed to the development and application of techniques in all areas of angiogenesis and lymphangiogenesis. Each chapter introduces and discusses one or a group of closely related techniques and convey step-by-step protocol information and detailed technical guidance to the reader. Emphasis has been placed on explanatory illustrations, critical technical steps as well as divulging information on the benefits and caveats of specific practices related to the methods discussed. This manual is intended to serve as a written guide for both newcomers and established professionals in the field.